Disease Background
Parkinson's disease (PD) is characterized by chronic neurodegeneration in the midbrain region of the brain affecting dopaminergic neurons. Greater than 500,000 Americans suffer from this progressive, debilitating disease. Current therapies affect symptoms, and there are no therapies that reverse or halt the motor dysfunction. Mixed results have been found with transplantation of fetal neural stem cells into the brains of PD patients, originally introduced in the late ’80s, however serious side effects, including dyskinesia have been observed. Other invasive, growth factor therapeutic approaches have been attempted, but with little success.

Overview of Neuronascent’s lead candidates: NNI-362 and NNI-370
Neuronascent has discovered non-invasive therapies that are neuro-restorative, in other words they promote the proliferation, migration, differentiation and ensure the survival of nascent neurons in the midbrain region, an area where neurons are selectively lost in Parkinson’s disease.

Our lead candidate for Alzheimer’s disease, NNI-362 is effective in promoting new neurons in a number of disease models and was shown to halt all further neuronal loss in a benchmark model of chronic, progressive Parkinson’s disease. Though the pilot study used a very short administration period, NNI-362 treatment already demonstrated a trend toward regeneration of neurons in the caudate putamen (see graph below). Further chronic administration is planned to determine if an IND for Parkinson’s should also be submitted, where the planned AD Phase1a safety trial in humans, could potentially be utilized for PD as well.

Our back-up therapeutic, NNI-370 was optimized from a completely separate and novel small molecule family and represents an exciting new class of potential therapies, that in vitro promotes new neuron growth from ventral midbrain stem cells and that inhibits neuron loss due to key initiators of dopaminergic neuron death. After optimizing the family of agents down to one efficacious therapeutic, we aim to test the agent in the chronic, progressive animal model that showed NNI-362 was efficacious.

Pilot Data for NNI-362 in a chronic progressive model of Parkinson’s disease. NNI-362 administered for just 2 weeks showed complete inhibition of all further neuron loss (left graph below), but also showed a trend for neuro-regeneration (right graph below) as had been seen for other disease models. All work was completed in Dr. Charles Meshul’s laboratory at the VA in Portland Oregon.